A candidate is thought for a two-year position (an extension is possible) to work on structural characterisation of respiratory complex I from T. thermophilus.
Complex I is central to bioenergetics – it is the first and largest enzyme of the respiratory chain in mitochondria and bacteria. It is also involved in a wide range of human diseases. We use the bacterial enzyme as a ‘minimal’ model of the more elaborate mammalian complex I. We have determined, by X-ray crystallography, all currently known atomic structures of complex I, starting with the hydrophilic domain (Science 2005, 2006), followed by the membrane domain (Nature 2010, 2011) and, finally, the recent (Nature 2013) structure of the entire Thermus thermophilus complex (536 kDa, 16 subunits, 9 Fe-S clusters, 64 TM helices). Structures suggest a unique mechanism of coupling between electron transfer in the hydrophilic domain and proton translocation in the membrane domain, via long-range (up to ~200 Å) conformational changes. In order to determine the intriguing coupling mechanism, we are now working on the structures of the complex in different redox states, with various bound substrates. We are also interested in establishing the mode of action of various inhibitors of complex I. The post holder will be involved in taking this challenging project further, which requires extensive experience in protein purification and X-ray crystallography, preferably acquired working with membrane proteins or macromolecular assemblies. The post is partly funded via collaboration with Pharma. Initially several months will be spent training in the MRC Mitochondrial Biology Unit in Cambridge, UK and then the project will be moved together with the rest of the group to the Institute of Science and Technology in Austria, near Vienna. IST Austria is a new institute dedicated to basic research, providing world-class research environment and benefits. We are looking to fill the post by early 2015. All queries and applications with CVs and names of 2-3 academic referees should be forwarded to Dr. Leonid Sazanov (saza...@mrc-mbu.cam.ac.uk).
